This is a broad program of research encompassing a range of problem areas and involving a diversity of experimental approaches. It is therefore important that this progress report be organized according to the conceptual framework of the program, which is described in the following outline. Progress within the various segments of the program is summarized in the succeeding project summaries and in more detail in the accompanying publications. PROGRAM AREA I: SEGMENTS UTILIZING CHEMICAL MODELS: A. Nitrosamines and Nitrosation Products. 1. Mutagenic Activity of Nitrosamines and Their Activation to Mutagens and Carcinogens; 2. Activation and Metabolism of Nitrosamines; 3. Chemical Activation of Nitroamines. B. Reactions of Peroxiding Lipids with Protein and Amino Acids. PROGRAM AREA II: SEGMENTS UTILIZING CELL CULTURES MODELS: A. Human and Other Cell Cultures; B. Bacterial Systems for Investigating DNA damage and repair. C. Regulatory efficiency of Intracellular Proteases in Virally and Chemically transformed cells. PROGRAM AREA III: SEGMENTS UTILIZING ANIMAL MODELS: A. Interactions Among Environmental Agents; B. Bioassays of Toxicity and Carcinogenicity. PROGRAM AREA IV: TISSUE RESPONSES AND SUBCELLULAR INTERACTIONS: A. Carcinogen Effects on Nuclear Function and Other Biochemical Processes; B. Carcinogen-Induced Modification of Cellular Macromolecules. PROGRAM AREA V: ADMINISTRATIVE AND SUPPORT ACTIVITIES: A. Mass Spectrometry Facility.